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Objective: The goal of this study was to compare patient-reported efficacy of suburothelial versus intradetrusor onabotulinumtoxin A (BTX-A) in patients with refractory overactive bladder (OAB). Ma...

Purpose Creating inclusive LGBTQ+ environments is important in the provision of inclusive care. This cross sectional study assessed whether patient intake forms in pediatric surgery departments were LGBTQ+ inclusive (L-I). Methods North American pediatric surgery departments affiliated with pediatric surgery fellowships or general surgery residencies were contacted to retrieve patient intake forms. Forms were assessed for LGBTQ+ inclusivity using a novel L -I scoring system consisting of 6 criteria: preferred name, pronouns, preferred language, gender identity, sex assigned at birth, and l -I guardianship. Institutions without intake forms were invited to comment on their use of l -I intake questions. Results 59/125 programs responded to our query, 10 of which provided intake forms. Median l -I score was 2/6 points (range 1–4). l -I guardianship was the most common question asked. No intake form asked for pronouns. Of the 49 institutions without forms, 30.5% reported asking l -I questions during initial visits. Narratives from these institutions varied widely. Some institutions supported routine l -I questions while others stated l -I questions were unnecessary, irrelevant, and/or offensive. Conclusions Few North American pediatric surgery departments consistently ask l -I questions during the intake process. Comments questioning the appropriateness and necessity of l -I questions highlight the need for LGBTQ+ education. Level of evidence Level III. Type of study Cross sectional study.

BACKGROUND: As treatments improve for colorectal cancer (CRC), interventions to improve quality of life and decrease long-term effects are needed. Physical activity (PA) is particularly important during cancer treatment because it may decrease treatment side effects, allow patients to more easily increase PA after treatment, and integrate with individuals’ motivation to make lifestyle changes after a cancer diagnosis. OBJECTIVES: This article aims to synthesize what is known about PA during CRC treatment. METHODS: A systematic literature search was conducted. Data were evaluated across 17 studies with a collective sample size of 1,184. Because of heterogeneity across studies, a narrative synthesis was conducted. FINDINGS: Studies included mostly college educated and married White men and women aged 50–60 years. Promising effects of PA were identified on several types of outcomes. The most common techniques to support PA included goal setting and providing instructions. The benefits of PA and how to best support PA during CRC treatment need to be better understood in future studies of racially and ethnically diverse patients with CRC.

Background AA living in rural areas of the southeastern U.S. experience a disproportionate burden of cardiovascular disease (CVD) morbidity and mortality. Neighborhood environmental factors contribute to this disparity and may decrease the effectiveness of lifestyle interventions aimed at preventing CVD. Furthermore, the influence of neighborhood factors on AA CVD risk behaviors (i.e. physical activity) may be obscured by the use of researcher-defined neighborhoods and researcher-defined healthy and unhealthy places. The objective of this study was to elucidate the effects of neighborhood environments on AA CVD risk behaviors among AA adults who recently completed a lifestyle intervention. We specifically sought to identify AA adults’ self-perceived places of significance and their perceptions of how these places impact CVD risk behaviors including diet, physical activity and smoking. Methods We conducted semi-structured interviews with AA adults (N = 26) living in two rural North Carolina counties (Edgecombe and Nash, North Carolina, USA). Participants were recruited from a community-based behavioral CVD risk reduction intervention. All had at least one risk factor for CVD. Participants identified significant places including where they spent the most time, meaningful places, and healthy and unhealthy places on local maps. Using these maps as a reference, participants described the impact of each location on their CVD risk behaviors. Data were transcribed verbatim and coded using NVivo 12. Results The average age of participants was 63 (SD = 10) and 92% were female. Places participants defined as meaningful and places where they spent the most time included churches and relatives’ homes. Healthy places included gyms and parks. Unhealthy places included fast food restaurants and relatives’ homes where unhealthy food was served. Place influenced CVD risk behaviors in multiple ways including through degree of perceived control over the environment, emotional attachment and loneliness, caretaking responsibilities, social pressures and social support. Conclusions As we seek to improve cardiovascular interventions for rural AA in the American South, it will be important to further assess the effect of significant places beyond place of residence. Strategies which leverage or modify behavioral influences within person-defined significant places may improve the reach and effectiveness of behavioral lifestyle interventions.

Tinius, RA, Blankenship, M, Maples, JM, Pitts, BC, Furgal, K, Norris, ES, Hoover, DL, Olenick, A, Lambert, J, and Cade, WT. Validity of the 6-minute walk test and Young Men's Christian Association (YMCA) submaximal cycle test during midpregnancy. J Strength Cond Res 35(11): 3236-3242, 2021-Submaximal exercise testing can be a feasible alternative to maximal testing within special populations to safely predict fitness levels; however, submaximal exercise testing has not been well-validated for use during pregnancy. The purpose of this study was to determine the concurrent validity of the 6-minute walk test (6MWT) and the YMCA submaximal cycle test (YMCAT) to predict V̇o2max in physically active women during midpregnancy. Thirty-seven (n = 37) pregnant women (22.1 ± 1.4 weeks' gestation) and 10 (n = 10) nonpregnant women participated in the study. Subjects completed a graded maximal treadmill test at 1 visit to measure maximal oxygen consumption (V̇o2max), and then subjects completed the 6MWT and YMCAT in randomized order during a separate visit. The predicted V̇o2max from each submaximal test were compared with the measured V̇o2max from the treadmill test to assess the validity of these tests during pregnancy. Among pregnant women, predicted V̇o2max from the YMCAT was not correlated to the measured V̇o2max (r = 0.14, p = 0.42), and the predicted V̇o2max from the 6MWT was only moderately correlated (r = 0.40, p = 0.016) to the measured V̇o2max. Among nonpregnant women, the predicted V̇o2max values from both the YMCAT and the 6MWT had strong correlations with the measured V̇o2max values (YMCAT: r = 0.71, p = 0.02; 6MWT: r = 0.80, p = 0.006). Neither test demonstrated concurrent validity among the pregnant sample. The main finding is that the YMCAT is not a valid method to estimate V̇o2max during midpregnancy (likely due to physiological changes in heart rate [HR] during pregnancy). The 6MWT has potential to be used clinically for estimating fitness as actual and predicted values did positively correlate, and it is not dependent on HR responses to exercise. However, if a precise measure of fitness is needed, then neither test appears to have strong validity for use during midpregnancy.

Background The number and characteristics of pre-exposure prophylaxis (PrEP) health care providers in the United States have not been reported. Methods We analyzed a national pharmacy database that included >90% of all prescriptions dispensed by retail pharmacies and 60%-86% dispensed by mail-order outlets. We estimated the number of PrEP providers by year, provider type, physician specialty, and geographic location. We also measured the Gini coefficients for the distribution of PrEP patients among providers. Results The number of PrEP providers increased from 9621 in 2014 to 65,822 in 2019. In 2019, 68.1% of PrEP providers were physicians. The proportion of nurse practitioners or physician assistants increased from 18.0% in 2014 to 29.7% in 2019. Among all the US health care providers, those who prescribed PrEP increased from 0.7% in 2014 to 4.3% in 2019. Among all general practice/family medicine physicians, the percentage of who prescribed PrEP increased from 1.8% in 2014 to 13.6% in 2019 and from 14.2% to 34.2% among infectious disease physicians. The ratio of PrEP providers to 100 persons with PrEP indications was lowest in the South with 4.4. The Gini coefficient for the distribution of PrEP patients among providers was 0.75 in 2019, with 50% of the PrEP patients prescribed PrEP by 2.2% of PrEP providers. Conclusions An increasing number of providers prescribed PrEP during 2014-2019. The South had the largest number of new HIV diagnoses and greatest need for HIV prevention but had less PrEP service capacity compared with other regions. Expanded access to PrEP services is needed in the United States.

INTRODUCTION A short floppy fundoplication has been the surgical dogma to prevent dysphagia and gas-bloat after laparoscopic fundoplication while adequately addressing gastroesophageal reflux disease. The literature on the ideal length of narrowing (LON) of the gastroesophageal junction after fundoplication is sparse. The functional luminal imaging probe (FLIP) can be used during anti-reflux surgery to produce a visual representation of the LON. We hypothesize that a longer LON provides relief of GERD symptoms, however worse dysphagia and gas-bloat. METHODS AND PROCEDURES Prospectively collected data was analyzed. Patients with FLIP measurements during laparoscopic fundoplication between August 2018 and December 2020 were included. FLIP measurements at the gastroesophageal junction were recorded without pneumoperitoneum at 40-mL balloon fill after fundoplication. Reflux Symptom Index (RSI), Gastroesophageal Reflux Disease-Health Related Quality of Life Questionnaire (GERD-HRQL), gas-bloat score, and Dysphagia Score were collected. Comparisons were made using Spearman correlation coefficients (r) and two-tailed Wilcoxon rank-sum tests, with statistical significance set at p

Kidney fibrosis constitutes the shared final pathway of nearly all chronic nephropathies, but biomarkers for the non-invasive assessment of kidney fibrosis are currently not available. To address this, we characterize five candidate biomarkers of kidney fibrosis: Cadherin-11 (CDH11), Sparc-related modular calcium binding protein-2 (SMOC2), Pigment epithelium-derived factor (PEDF), Matrix-Gla protein, and Thrombospondin-2. Gene expression profiles in single-cell and single-nucleus RNA-sequencing (sc/snRNA-seq) datasets from rodent models of fibrosis and human chronic kidney disease (CKD) were explored, and Luminex-based assays for each biomarker were developed. Plasma and urine biomarker levels were measured using independent prospective cohorts of CKD: the Boston Kidney Biopsy Cohort, a cohort of individuals with biopsy-confirmed semiquantitative assessment of kidney fibrosis, and the Seattle Kidney Study, a cohort of patients with common forms of CKD. Ordinal logistic regression and Cox proportional hazards regression models were used to test associations of biomarkers with interstitial fibrosis and tubular atrophy and progression to end-stage kidney disease and death, respectively. Sc/snRNA-seq data confirmed cell-specific expression of biomarker genes in fibroblasts. After multivariable adjustment, higher levels of plasma CDH11, SMOC2, and PEDF and urinary CDH11 and PEDF were significantly associated with increasing severity of interstitial fibrosis and tubular atrophy in the Boston Kidney Biopsy Cohort. In both cohorts, higher levels of plasma and urinary SMOC2 and urinary CDH11 were independently associated with progression to end-stage kidney disease. Higher levels of urinary PEDF associated with end-stage kidney disease in the Seattle Kidney Study, with a similar signal in the Boston Kidney Biopsy Cohort, although the latter narrowly missed statistical significance. Thus, we identified CDH11, SMOC2, and PEDF as promising non-invasive biomarkers of kidney fibrosis.

Background Combination CDK4/6 inhibitor and endocrine therapy has been shown to significantly improve progression‐free survival (PFS) in patients with hormone receptor (HR)‐positive, HER2‐negative metastatic breast cancer (mBC). The aim of this retrospective study was to evaluate the real‐world benefit of first‐line combination therapy in this cohort and to correlate treatment efficacy with neutropenia, a common toxicity of CDK4/6 inhibitors. Methods This study included HR‐positive, HER2‐negative advanced or mBC patients who were treated with palbociclib plus endocrine therapy, mainly letrozole, between 1 January 2015 and 1 March 2018. Progression‐free survival (PFS) was determined using Kaplan–Meier analysis. The predictive value of absolute neutrophil count (ANC) and neutrophil‐to‐lymphocyte ratio (NLR) for PFS were explored using Cox regression models. Both ANC and NLR were used as a time‐dependent variable. Results In total, 165 patients were included with median PFS of 24.19 months (95% CI 18.93–NR). Median PFS for patients with bone‐only metastases (n = 54) was not reached (95% CI 18.21–NR). Among patients with all other metastases (n = 111), median PFS was 24.19 months (95% CI 16.33–33.82). Lower ANC was correlated with decreased risk of progression (HR 0.84, 95% CI 0.71–0.97, p = 0.008). There was no significant association between NLR and the risk of disease progression (HR 1.07, 95% CI 0.97–1.18, p = 0.203). Conclusion The effectiveness of palbociclib and endocrine therapy in the treatment of HR‐positive, HER2‐negative mBC in the real‐world setting is similar to the efficacy reported in the PALOMA‐2 trial. Patients with lower neutrophil count may have a lower risk of early disease progression., The real‐world benefit of combination CDK4/6 inhibitor and endocrine therapy is similar to that reported in clinical trials. Treatment‐related neutropenia, assessed by absolute neutrophil count (ANC), may be correlated with lower risk of disease progression and a lower ANC threshold for dose reduction may be warranted.

Author(s): Savarirayan, Ravi; Tofts, Louise; Irving, Melita; Wilcox, William R; Bacino, Carlos A; Hoover-Fong, Julie; Font, Rosendo Ullot; Harmatz, Paul; Rutsch, Frank; Bober, Michael B; Polgreen, Lynda E; Ginebreda, Ignacio; Mohnike, Klaus; Charrow, Joel; Hoernschemeyer, Daniel; Ozono, Keiichi; Alanay, Yasemin; Arundel, Paul; Kotani, Yumiko; Yasui, Natsuo; White, Klane K; Saal, Howard M; Leiva-Gea, Antonio; Luna-Gonzalez, Felipe; Mochizuki, Hiroshi; Basel, Donald; Porco, Dania M; Jayaram, Kala; Fisheleva, Elena; Huntsman-Labed, Alice; Day, Jonathan RS | Abstract: PurposeAchondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported.MethodsAfter completing at least six months of a baseline observational growth study, and 52 weeks in a double-blind, placebo-controlled study, participants were eligible to continue treatment in an open-label extension study, where all participants received vosoritide at a dose of 15.0 μg/kg/day.ResultsIn children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected.ConclusionVosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia treated daily for two years.

Vosoritide, an analog of C-type natriuretic peptide, has been developed for the treatment of children with achondroplasia. The pharmacokinetics of vosoritide and relationships between plasma exposure and efficacy, biomarkers, and safety endpoints were evaluated in a phase II, open-label, dose-escalation study (N = 35 patients aged 5–14 years who received daily subcutaneous injections for 24 months) and a phase III, double-blind, placebo-controlled study (N = 60 patients aged 5–18 years randomized to receive daily subcutaneous injections for 52 weeks). Pharmacokinetic parameters for both studies were obtained from non-compartmental analysis. Potential correlations between vosoritide exposure and changes in annualized growth velocity, collagen type X marker (CXM; a biomarker of endochondral ossification), cyclic guanosine monophosphate (cGMP; a biomarker of pharmacological activity), heart rate, and systolic and diastolic blood pressures were then evaluated. The exposure–response relationships for changes in both annualized growth velocity and the CXM biomarker saturated at 15 μg/kg, while systemic pharmacological activity, as measured by urinary cGMP, was near maximal or saturated at exposures obtained at the highest dose studied (i.e. 30 μg/kg). This suggested that the additional bioactivity was likely in tissues not related to endochondral bone formation. In the phase III study, following subcutaneous administration at the recommended dose of 15 μg/kg to patients with achondroplasia aged 5–18 years, vosoritide was rapidly absorbed with a median time to maximal plasma concentration (Cmax) of 15 minutes, and cleared with a mean half-life of 27.9 minutes after 52 weeks of treatment. Vosoritide exposure (Cmax and area under the concentration-time curve [AUC]) was consistent across visits. No evidence of accumulation with once-daily dosing was observed. Total anti-vosoritide antibody (TAb) responses were detected in the serum of 25 of 60 (42%) treated patients in the phase III study, with no apparent impact of TAb development noted on annualized growth velocity or vosoritide exposure. Across the exposure range obtained with 15 µg/kg in the phase III study, no meaningful correlations between vosoritide plasma exposure and changes in annualized growth velocity or CXM, or changes from predose heart rate, and systolic or diastolic blood pressures were observed. The results support the recommended dose of vosoritide 15 µg/kg for once-daily subcutaneous administration in patients with achondroplasia aged ≥ 5 years whose epiphyses are not closed. NCT02055157, NCT03197766, and NCT01603095.

Pediatrician Screening, Brief Intervention, and Referral to Treatment (SBIRT) practices vary widely, though little is known about the correlates of SBIRT implementation. Using data from a national sample of US pediatricians who treat adolescents (n = 250), we characterized self-reported utilization rates of SBIRT among US pediatricians and identified provider- and practice-level characteristics and barriers associated with SBIRT utilization. All participants completed an electronic survey querying the demographics, practice patterns, and perceived barriers related to SBIRT practices. Our results showed that 88% of respondents reported screening for substance use annually, but only 26% used structured/validated screening instruments. Furthermore, 40% of respondents provided evidence-based brief interventions, and only 11% implemented all core SBIRT practices. Common barriers (eg, confidentiality and insufficient time) and unique provider- and setting-specific barriers to implementation were identified. These findings indicate that although most pediatricians deliver some SBIRT components in their practice, few implement the full SBIRT model, and barriers persist.

Frequency modulation (FM) detection at low modulation frequencies is commonly used as an index of temporal fine-structure processing. The present study evaluated the rate of improvement in monaural and dichotic FM across a range of test parameters. In experiment I, dichotic and monaural FM detection was measured as a function of duration and modulator starting phase. Dichotic FM thresholds were lower than monaural FM thresholds and the modulator starting phase had no effect on detection. Experiment II measured monaural FM detection for signals that differed in modulation rate and duration such that the improvement with duration in seconds (carrier) or cycles (modulator) was compared. Monaural FM detection improved monotonically with the number of modulation cycles, suggesting that the modulator is extracted prior to detection. Experiment III measured dichotic FM detection for shorter signal durations to test the hypothesis that dichotic FM relies primarily on the signal onset. The rate of improvement decreased as duration increased, which is consistent with the use of primarily onset cues for the detection of dichotic FM. These results establish that improvement with duration occurs as a function of the modulation cycles at a rate consistent with the independent-samples model for monaural FM, but later cycles contribute less to detection in dichotic FM.

Introduction: Thyroglossal duct cysts (TGDCs) are the most common form of congenital neck cysts. They may become infected causing dysphagia or respiratory distress. Accordingly, the treatment is always surgical removal. Objectives: The objectives of this article were to examine complications following TGDC excision by surgical specialty, demographics, and comorbid conditions. Methods: A retrospective review of the National Surgical Quality Improvement Program database was performed. Pediatric cases from January 1, 2014 to November 1, 2015 with a current procedure terminology code of 60,280 (excision of TGDC or sinus) were included. Statistical analysis was performed to assess associations between complications and surgical specialty, demographics, and comorbidities. Results: Of the 867 cases that met inclusion criteria, the median age was 4 years. There were 448 males (52.3%) and 408 females (47.7%). Thirty-six patients (4.2%) experienced at least one 30-day complication. The most predominant complications were reoperation (19 patients, 2.2%), readmission (18 patients, 2.1%), and surgical site infection (16 patients, 1.9%). There was no statistically significant difference between complications and surgical specialty. In those experiencing a complication, there was a statistically significant difference between males (86.1%) and females (13.9%). Of patients with at least one comorbidity, 36.67% had a complication, while 17.22% did not have a complication. There was also a statistically significant difference in the percentage of patients with a past medical history of asthma between those with at least one complication (16.67%) compared to those without any complications (4.76%). Conclusions: excision is a generally safe procedure across surgical specialties. There is a higher complication rate in males compared to females as well as those with a history of at least one medical comorbidity and those with asthma. The most common 30-day complications are reoperation, readmission, and surgical site infection.

Background: The influence of prenatal diethylstilbestrol (DES) exposure on cancer incidence among middle-aged men has not been well-characterized. We investigated whether exposure to DES before birth impacts overall cancer risk, and risk of site-specific cancers. Methods: Men (mean age in 2016 = 62.0 years) who were or were not prenatally DES exposed were identified between 1953 and 1994 and followed for cancer primarily via questionnaire approximately every 5 years between 1994 and 2016. The overall and site-specific cancer rates of the two groups were compared using Poisson regression and proportional hazards modeling with adjustment for age. Results: DES exposure was not associated with either overall cancer [hazard ratio (HR), 0.94; 95% confidence interval (CI), 0.77–1.15] or total prostate cancer rates (HR, 0.95; 95% CI, 0.68–1.33), but was inversely associated with urinary tract cancer incidence (HR, 0.48; 95% CI, 0.23–1.00). Conclusions: There was no increase in either overall or prostate cancer rates among men prenatally DES exposed relative to those unexposed. An unexpected risk reduction was observed for urinary system cancers among the exposed relative to those unexposed. These findings suggest that prenatal DES exposure is unlikely to be an important contributor to cancer development in middle-aged men. Impact: The results of this study could lend reassurance to middle-aged men who were prenatally DES exposed that their exposure does not adversely influence their overall cancer risk.

We aim to analyze survival outcomes for sentinel lymph node biopsy (SLNB) versus axillary lymph node dissection (ALND) in human epidermal growth factor receptor (HER2)+ infiltrative ductal carcinoma (IDC) that demonstrate complete clinical response (cCR) to neoadjuvant systemic therapy (NAST) after initial presentation with clinical N1 (cN1) disease. NCDB 2004–2017 was utilized for the analysis. Female patients with unilateral HER2+ IDC, stage cT1–T4 cN1, who demonstrated cCR to NAST with reported definitive axillary surgical management were included. Patients were propensity score matched, and overall survival (OS) was compared. Cox regression analysis was used to identify survival predictors. 6453 patients were selected, of whom 2461 (38.1%) had SLNB and 3992 (69.1%) had ALND as definitive axillary surgical management. The trend of SLNB utilization increased from 20% in 2012 to 50% in 2017. A total of 2454 patients were matched from each group with adequate adjustment for all variables. There was no difference in OS between SLNB versus ALND (84.03 ± 0.36 versus 84.62 ± 0.42 months; p = 0.522). Cox regression identified age, cT stage, primary tumor response to NAST, ypN+, and endocrine therapy as significant OS predictors. In subgroup analysis of patients with ypN+ who had SLNB as a definitive procedure, primary tumor response to NAST and continuation of adjuvant chemotherapy were associated with improved OS. In cN1 HER2+ IDC patients who demonstrate cCR to NAST, SLNB is a reasonable definitive procedure for axillary management with comparable OS outcomes to ALND. However, higher-level data are required to determine the appropriate management in the case of ypN+.

BACKGROUND: Children of parents with substance use disorders are at greater risk for mental and physical health co-morbidities. Despite guidelines, pediatricians rarely screen for substance use in the family/household, citing fear of offending parents. The objectives of this study were to examine 1) caregiver acceptance of pediatricians screening for family/household substance use during well-child visits, 2) prevalence of family/household substance use, and 3) the association between family/household substance use and trust in their child’s pediatrician. METHODS: This cross-sectional study surveyed adult caregivers presenting a child for medical care at two urban pediatric outpatient clinics using a brief anonymous computer-based survey. The primary outcome measured acceptability of pediatrician screening for family/household substance use. Substance use and concerns about use in the family/household were also assessed. RESULTS: Adult caregivers (N=271) surveyed were mean age 35 years, 73% mothers, 90% African American, and 85% on Medicaid. Over half (51%) of caregivers reported substance use by someone in the family/household, most commonly cigarettes (38%), followed by alcohol (19%) and marijuana (10%). Sixty-one percent of caregivers who reported family substance use, expressed concern about use of this substance. The majority (87%) agreed it is appropriate for pediatricians to ask caregivers about family/household substance use. No differences were found between caregivers who did and did not report substance use in their family/household. Caregivers with concerning substance use in their family/household were less likely to trust their pediatrician [OR=0.21, 95%CI:0.05, 0.85] CONCLUSIONS: Caregivers endorsed acceptance of universal screening for substance use, including illicit substances, and substance use disorders in the family/household during well-child visits. Pediatricians are trusted professionals with expertise in communicating with parents to maximize the health of their patients; assessing family history of substance use and substance use disorders is a natural extension of their role.

Highlights • This paper evaluated lesion-directed prostatic high dose rate brachytherapy. • Lesions defined by prostate specific membrane antigen positron emission tomography. • Dose escalation was confirmed using whole-mount digital histology. • Targeting lesions led to significantly higher dose to high-grade histologic cancer., Background and purpose Prostate specific membrane antigen positron emission tomography imaging (PSMA-PET) has demonstrated potential for intra-prostatic lesion localization. We leveraged our existing database of co-registered PSMA-PET imaging with cross sectional digitized pathology to model dose coverage of histologically-defined prostate cancer when tailoring brachytherapy dose escalation based on PSMA-PET imaging. Materials and methods Using a previously-developed automated approach, we created segmentation volumes delineating underlying dominant intraprostatic lesions for ten men with co-registered pathology-imaging datasets. To simulate realistic high-dose-rate brachytherapy (HDR-BT) treatments, we registered the PSMA-PET-defined segmentation volumes and underlying cancer to 3D trans-rectal ultrasound images of HDR-BT cases where 15 Gray (Gy) was delivered. We applied dose/volume optimization to focally target the dominant intraprostatic lesion identified on PSMA-PET. We then compared histopathology dose for all high-grade cancer within whole-gland treatment plans versus PSMA-PET-targeted plans. Histopathology dose was analyzed for all clinically significant cancer with a Gleason score of 7or greater. Results The standard whole-gland plans achieved a median [interquartile range] D98 of 15.2 [13.8–16.4] Gy to the histologically-defined cancer, while the targeted plans achieved a significantly higher D98 of 16.5 [15.0–19.0] Gy (p = 0.007). Conclusion This study is the first to use digital histology to confirm the effectiveness of PSMA-PET HDR-BT dose escalation using automatically generated contours. Based on the findings of this study, PSMA-PET lesion dose escalation can lead to increased dose to the ground truth histologically defined cancer.

Hydration plays an important role in performance, injury prevention, and recovery for athletes engaged in competitive sports. Therefore, it is important that strength and conditioning coaches understand an athlete’s hydration needs to prevent illness and enhance performance. The purpose of this study was to identify hydration knowledge, attitudes, and behaviors of collegiate track and field throwers, as well as identify barriers to hydration and sources of nutritional information. The Rehydration and Refueling in Collegiate Track and Field Throwers Survey was sent to 271 track and field thrower coaches with a request to forward the email to current track and field throwers. Pearson correlation coefficients were calculated regarding knowledge, attitude, and behavior scores among the participants in this sample. Differences among response patterns were assessed via Chi-square analysis. Alpha level was set at p = .05. Results demonstrated that 97.3% (n = 287) of respondents knew that dehydration would decrease performance, but 50.5% (n = 149) erroneously believed thirst was the best indicator of dehydration. Chi-square analysis demonstrated a significant difference in reported values between participants who intended to eat a performance-enhancing diet and those who consumed less fluid than recomended values (207 – 295 m)l in the 2-3 hours prior to competition (χ2 = 10.87, p < .05). Pearson correlation coefficients demonstrated a large association between knowledge and behavior (r = .70, p < .05), a medium association between knowledge and attitude (r = .41, p < .05), and a small association between attitude and behavior (r = .21, p < .05). This suggests that strength and conditioning coaches and health staff need to educate and monitor hydration behaviors among collegiate track and field throwers to optimize performance.

HIV testing is a critical component of effective HIV prevention and care. CDC recommends routine opt-out HIV testing in health care settings for all sexually active persons aged 13-64 years at least once in their lifetime and risk-based testing regardless of age for those who report behaviors associated with HIV acquisition (1). However, recent studies show low HIV testing rates in clinical settings; HIV testing rates at visits to physician offices did not increase during 2009-2016 (2). The objective of the current study is to estimate temporal trends in HIV testing among persons with commercial insurance or Medicaid from 2014 through 2019 and describe their demographic characteristics in 2019. Weighted data from the IBM MarketScan Commercial Claims and Encounters database* (commercial insurance) and from the Centers for Medicare & Medicaid Services (CMS) claims database† (Medicaid) were analyzed to estimate the proportions of persons with commercial insurance or Medicaid who received testing for HIV. Testing rates increased among male and nonpregnant female persons aged ≥13 years with either type of coverage. In 2019, only 4.0% of those with commercial insurance and 5.5% of those with Medicaid received testing for HIV. Testing rates were higher among non-Hispanic Black or African American (Black) persons and Hispanic or Latino (Hispanic) persons. Based on mathematical modeling studies, these annual testing rates would need to increase at least threefold and be sustained over several years (3,4) to achieve the Ending the HIV Epidemic (EHE) in the U.S. initiative goal of ≥95% of persons with HIV being aware of their infection by 2025.§ Interventions need to be implemented to increase routine and risk-based HIV testing in clinical settings to higher levels that can help reduce disparities in HIV diagnoses between Black and Hispanic persons compared with non-Hispanic White (White) persons (5). Increased HIV testing is essential to achieve the goals of the EHE initiative and reduce disparities in HIV diagnoses; public health should partner with health care systems to implement interventions that support increased testing.

PURPOSE To complete a systematic review to identify evidence of the effectiveness of informal caregiver training with functional mobility tasks for patients with neurological diagnoses routinely completed by physical therapists (PTs). METHODS Databases searched: PubMed, PEDro, CINAHL, Web of Science, Proquest Health and Medical, and Scopus. Authors included studies with adult patients requiring assistance with functional mobility due to a neurological diagnosis, with the care provided by informal caregivers. Authors excluded studies with paid caregivers, or patient diagnoses of human immunodeficiency virus, dementia, or cancer. Data extracted included type of study, methodological quality review (using Downs and Black scale), number of subjects, outcome measures, interventions, and main results. RESULTS Of 2372 total articles screened, 36 full-text articles were analyzed, with seven articles identified for inclusion in the review. All studies showed variability in number of subjects, methods, interventions, outcome measures, and results. Four of the studies showed positive results from the training of informal caregivers. CONCLUSIONS While there is initial evidence that training informal caregivers in physical mobility tasks may help to lessen caregiver burden, further investigation is warranted. The topics typically addressed by PTs with informal caregiver training, such as transfers and ambulation, have not been extensively studied in the literature.Implications for rehabilitationPhysical therapists routinely complete training for caregivers on functional mobility tasks, with some initial evidence of the effectiveness of this training.Training for informal caregivers assisting individuals with neurological conditions has the potential to reduce injuries and decrease caregiver burden.Rehabilitation professionals should implement effective training methods for caregivers, resulting in a safer home environment for individuals with neurological diagnoses.

Background Approximately 24% of physical therapists report regularly using yoga to strengthen major muscle groups. Although clinicians and athletes often use yoga as a form of strength training, little is known about the activation of specific muscle groups during yoga poses, including the gluteus maximus and medius. Hypothesis/Purpose The purpose of this study was to measure gluteus maximimus and gluteus medius activation via electromyography (EMG) during five common yoga poses. A secondary purpose of the current study was to examine differences in muscle activation between sexes and experience levels. Study Design Cross-Sectional Methods Thirty-one healthy males and females aged 18-35 years were tested during five yoga poses performed in a randomized order. Surface EMG electrodes were placed on subjects’ right gluteus maximus and gluteus medius. Subjects performed the poses on both sides following a maximal voluntary isometric contraction (MVIC) test for each muscle. All yoga pose EMG data were normalized to the corresponding muscle MVIC data. Results Highest gluteus maximus activation occurred during Half Moon Pose on the lifted/back leg (63.3% MVIC), followed by the stance/front leg during Half Moon Pose (61.7%), then the lifted/back leg during Warrior Three Pose (46.1%). Highest gluteus medius activation occurred during Half Moon Pose on the lifted/back leg (41.9%), followed by the lifted/back leg during the Warrior Three Pose (41.6%). A significant difference was found in %MVIC of gluteus medius activity between male and female subjects (p = 0.026), and between experienced and inexperienced subjects (p = 0.050), indicating higher activation among males and inexperienced subjects, respectively. Conclusion Half Moon Pose and Warrior Three Pose elicited the highest activation for both the gluteus maximus and the gluteus medius. Higher gluteus medius activation was seen in males and inexperienced subjects compared to their female and experienced counterparts. Level of Evidence 3

OBJECTIVE The authors sought to determine the overall incidence of cervicomedullary decompression (CMD) in patients with achondroplasia and the characteristics associated with those surgeries across multiple institutions with experience caring for individuals with skeletal dysplasias. METHODS Data from CLARITY (Achondroplasia Natural History Study) for 1374 patients with achondroplasia from four skeletal dysplasia centers (A. I. duPont Hospital for Children, Johns Hopkins University, University of Texas Health, and University of Wisconsin School of Medicine and Public Health) followed from 1957 to 2017 were recorded in a Research Electronic Data Capture (REDCap) database. Data collected and analyzed included surgeries, indications, complications, ages at time of procedures, screening procedures, and medical diagnoses. RESULTS There were 314 CMD procedures in 281 patients (20.5% of the entire cohort). The median age of first CMD was 1.3 years in males and 1.1 years in females. Over time, there was a decrease in the median age of patients at first CMD. All patients born before 1980 who underwent CMD had the procedure after 5 years of age, whereas 98% of patients born after 2010 underwent CMD before 5 years of age. In addition, a greater proportion of patients born in more recent decades had documented neuroimaging and polysomnography (PSG) prior to CMD. Ventriculoperitoneal shunts (VPSs) were placed more frequently in patients undergoing CMD (23%) than in the entire cohort (8%). Patients who required either CMD or VPS were 7 times more likely to require both surgeries than patients who required neither surgery (OR 7.0, 95% CI 4.66–10.53; p < 0.0001). Overall, 10.3% of patients who underwent CMD required a subsequent CMD. CONCLUSIONS The prevalence of CMD in this large achondroplasia cohort was 20%, with more recently treated patients undergoing first CMD at younger ages than earlier patients. The use of neuroimaging and PSG screening modalities increased over time, suggesting that increased and better surveillance contributed to earlier identification and intervention in patients with cervicomedullary stenosis and its complications.

BACKGROUND Frailty may occur at younger ages among HIV+ populations. We evaluated associations of the frailty status with self-reported single and recurrent falls in the Women's Interagency HIV Study (WIHS). METHODS The frailty status was defined using the Fried Frailty Phenotype (FFP) among 897 HIV+ and 392 HIV- women; median age 53 years. Women were classified as robust (FFP 0), prefrail (FFP 1-2), and frail (FFP 3-5). Stepwise logistic regression models adjusting for the HIV status and study site were fit to evaluate associations of the FFP with self-reported single (1 vs. 0) and recurrent falls (≥2 vs. 0) over the prior 12 months. RESULTS HIV+ women were less likely to be frail (9% vs. 14% vs. P = 0.009), but frequency of falls did not differ by the HIV status. In multivariate analyses, recurrent falls were more common among prefrail [adjusted odds ratio (AOR) 2.23, 95% confidence interval (CI): 1.40 to 3.57, P = 0.0008] and frail (AOR 3.61, 95% CI: 1.90 to 6.89, P < 0.0001) than robust women. Among HIV+ women, single (AOR 2.88, 95% CI: 1.16 to 7.20, P = 0.023) and recurrent falls (AOR 3.50, 95% CI: 1.24 to 9.88, P = 0.018) were more common among those who were frail; recurrent, but not single falls, were more common among prefrail than robust HIV+ women (AOR 2.00, 95% CI: 1.03 to 3.91, P = 0.042). CONCLUSIONS HIV+ women were less likely to be frail. Compared with robust women, prefrail and frail women with and without HIV were more likely to experience single or recurrent falls within a 12-month period. Additional studies are needed to develop interventions that decrease development of frailty and reduce risk of recurrent falls among HIV+ women.

Hearing loss is associated with higher health care spending and use, but little is known about the unmet health care needs of people with hearing loss or difficulty. Analysis of 2016 Medicare Current Beneficiary Survey data for beneficiaries ages sixty-five and older reveals that those who reported a lot of trouble hearing in the past year were 49 percent more likely than those who reported no trouble hearing to indicate not having a usual source of care. Compared with those who reported no trouble hearing, those who reported some trouble hearing were more likely to indicate not having obtained medical care in the past year when they thought it was needed, as well as not filling a prescription, with the risk for both behaviors being greater among those reporting a lot of trouble hearing versus a little. Interventions that improve access to hearing services and aid communication may help older Medicare beneficiaries meet their health care needs.

Introduction. Choice of adjuvant therapy for high risk endometrial cancers is controversial. The so-called “sandwich” regimen of pelvic external beam radiation administered between cycles of Carboplatin/Paclitaxel (CT-RT-CT) is commonly used in clinical practice but has not been evaluated in randomized endometrial cancer trials. There is relatively little published data regarding toxicity, patient tolerance, and efficacy of this regimen. Here, we report our institutional experience of CT-RT-CT for locally advanced endometrial cancer, focusing on toxicity and rates of compliance with study therapy. Material and methods. Medical records of consecutive patients treated for surgically staged endometrial cancer at a tertiary care academic medical center between 2010 and 2017 were reviewed. All patients received adjuvant CT-RT-CT. Progression-free and overall survival were recorded from the date of surgery. Toxicity data was obtained from patient medical records and graded according to Common Terminology for Adverse Events Criteria, version 3.0. Results. Thirty-eight patients with histologically proven stage I–IV endometrial cancer were included. Eighty-four percent of patients were able to complete all 6 planned cycles of chemotherapy and 92% completed at least 4 cycles. Cumulative incidence of grade 3–4 hematologic toxicity was 55%. Locoregional recurrence was the first site of failure in 2 patients (5.1%) while distant failure was the first site of recurrence in 8 patients (21%). Two year overall survival and progression-free survival were 76% and 77% respectively. Conclusion. Our results suggest that adjuvant chemotherapy and radiation therapy with the “sandwich” regimen is associated with acceptable toxicity and satisfactory rates of completion of planned therapy.

The average age at menarche declined in European and U.S. populations during the 19th and 20th centuries. The timing of pubertal events may have broad implications for chronic disease risks in aging women. Here we tested for associations of recalled menarcheal age with risks of 19 cancers in 536,450 women [median age, 60 years (range, 31–39 years)] in nine prospective U.S. and European cohorts that enrolled participants from 1981 to 1998. Cox regression estimated multivariable-adjusted HRs and 95% confidence intervals (CI) for associations of the age at menarche with risk of each cancer in each cohort and random-effects meta-analysis was used to generate summary estimates for each cancer. Over a median 10 years of follow-up, 60,968 women were diagnosed with a first primary incident cancer. Inverse linear associations were observed for seven of 19 cancers studied. Each additional year in the age at menarche was associated with reduced risks of endometrial cancer (HR = 0.91; 95% CI, 0.89–0.94), liver cancer (HR = 0.92; 95% CI, 0.85–0.99), melanoma (HR = 0.95; 95% CI, 0.93–0.98), bladder cancer (HR = 0.96; 95% CI, 0.93–0.99), and cancers of the colon (HR = 0.97; 95% CI, 0.96–0.99), lung (HR = 0.98; 95% CI, 0.96–0.99), and breast (HR = 0.98; 95% CI, 0.93–0.99). All but one of these associations remained statistically significant following adjustment for baseline body mass index. Similarities in the observed associations between menarche and seven cancers suggest shared underlying causes rooted early in life. We propose as a testable hypothesis that early exposure to sex hormones increases mid-life cancer risks by altering functional capacities of stem cells with roles in systemic energy balance and tissue homeostasis. Significance: Age at menarche is associated with risk for seven cancers in middle-aged women, and understanding the shared underlying causal pathways across these cancers may suggest new avenues for cancer prevention.

22q11.2 microdeletion syndrome (22q11.2DS) is a common genetic condition associated with structural and functional velopharyngeal anomalies. However, not all patients with 22q11.2DS presenting for treatment will have an established diagnosis and/or have been evaluated for critical medical comorbidities including congenital cardiovascular anomalies, bleeding diatheses, hypocalcemia, and cervical spine instability. When considering surgical management for patients with velopharyngeal insufficiency (VPI), it is imperative to be aware of the clinical features of 22q11.2DS to avoid serious morbidity and mortality. This is illustrated here with 2 case examples. First, a 10-year-old male with 22q11.2DS presented at 6 years old for treatment of VPI associated with submucous cleft palate. Preoperative computed tomographic angiography revealed right carotid artery tortuosity and retropharyngeal displacement, while intraoperative Doppler ultrasound confirmed carotid artery medialization at the base of the proposed flap. Consequently, he underwent Furlow palatoplasty instead of pharyngeal flap. Second, a 5-year-old male with 22q11.2DS presented at 4 years old for treatment of VPI. Palatal lengthening with double-opposing buccal flaps was performed to mitigate the risk for carotid artery injury, need for preoperative imaging, and risk for developing obstructive sleep apnea (OSA). Right carotid artery medialization was seen intraoperatively as marked pulsations. Both patients underwent cardiac and anesthesia evaluations prior to surgery given their histories of congenital heart defects (CHD) and prior postoperative hypocalcemia.

Radiofrequency (RF) energy has been delivered in a variety of methods to the vagina, bladder, and periurethral tissue to improve myriad genitourinary complaints. Currently, practitioners are promoting transvaginal RF treatments with a minimal understanding of the various platforms and data to support or refute their utilization. This review explores how various RF technologies create desired tissue effects, review the published literature reporting outcomes of various treatment regimes, and peer into potential future uses of this technology in urogynecology. A comprehensive literature review was performed for articles pertaining to RF energy use in women for genitourinary complaints with regard to stress urinary incontinence (SUI), genitourinary syndrome of menopause (GSM), female sexual dysfunction (FSD), and overactive bladder (OAB). Radiofrequency energy devices heat tissues via direct or micro-needling applications with the goal of stimulating collagen remodeling, neovascularization, and potentially modulation of nerve function. By altering the approach and location of energy application, many new devices have been marketed for treatment of conditions such as SUI, GSM, FSD, and OAB. Available studies demonstrate promising efficacy and favorable safety; however, interpretation of studies is greatly limited by poor study quality and reporting. Despite a lack of high-quality evidence for efficacy, safety, and durability in the literature, practitioners around the world continue to promote RF technology for a variety of genitourinary complaints. Currently, it appears that RF energy can potentially treat a variety of genitourinary conditions, but more robust data are needed to substantiate evidence-based use.

PURPOSE To determine effectiveness of a transcutaneous electrical nerve stimulation (TENS) unit to improve labor pain management and patient satisfaction with overall labor experience among women in labor at term. STUDY DESIGN Prospective, exploratory design using convenience sampling. METHODS Pregnant women at term, anticipating a vaginal birth at our tertiary care hospital, were invited to participate in the TENS study to help manage early labor pain. Pain level was assessed on entry into the study and 2 hours post-TENS application using the Wong-Baker FACES® Pain Rating Scale. A TENS satisfaction survey was conducted during postpartum. Pain scores were analyzed using a matched Wilcoxon signed-rank test. RESULTS There were 272 women enrolled in the study; 255 completed the patient satisfaction survey and 263 had measured pain assessments pre- and post-TENS application. There was a significant reduction in pain scores after application of TENS, (7.09 vs. 6.74, p = 0.02). Most women 78% (199/255) agreed that TENS helped manage early labor pain, 80% (203/255) would recommend TENS for management of early labor pain, and 72% (183/255) would use TENS again. CLINICAL IMPLICATIONS TENS therapy provides nurses with an opportunity to offer women a low-cost, low-intervention treatment for managing early labor. TENS provides a distraction from contractions and generates a sense of control to help women manage the discomforts of labor and possibly remain home longer.

The Endoluminal Functional Imaging Probe (EndoFLIP, Medtronic, Minneapolis, MN) impedance planimetry system provides real-time three-dimensional images of gastrointestinal sphincters of interest, particularly the esophagogastric junction. This allows for real-time objective measurements during the surgical management of foregut diseases such as gastroesophageal reflux and achalasia. Literature continues to grow on how to best utilize this recent technology to improve patient outcomes. This outlines the intraoperative utilization of EndoFLIP.

Background: Patient recovery following alternative-access transcatheter aortic valve replacement (TAVR) via transcarotid (TC) and transthoracic (TT; transapical or transaortic) access has not been ...

Adenomatous Polyposis Coli (APC) is a multi-domain tumor suppressor with multiple binding partners, including β-catenin, axin, and microtubules. APC is lost in many epithelial cancers, including up to 70% of sporadic breast cancers, with a tendency towards triple negative breast cancers (TNBCs). We previously demonstrated that APC knockdown in the human TNBC cell line, MDA-MB-157, resulted in resistance to Paclitaxel (PTX), a chemotherapeutic agent of the Taxane family that inhibits mitotic progression. Further studies have confirmed this finding in the MDA-MB-231 cells with CRISPR-mediated APC knockout. To understand the mechanism(s) by which APC controls response to PTX, we have taken two approaches. We first performed an unbiased analysis of transcriptomic changes downstream of APC loss to identify potential therapeutic targets to overcome PTX resistance. In this, a group of transcripts involved in regulation of the cell cycle were identified, including LBH, GLI1, RGS4, and NUPR1. These results have been validated by qRT-PCR and western blot, leading to studies in the laboratory to investigate their specific effects on the response to PTX in breast cancer. Along with the broad exploration studies, molecular studies have focused on whether APC controls expression of cell cycle proteins, leading to PTX resistance. While we observed changes in multiple cell cycle proteins, our focus was on the G2/M transition, given that both PTX and APC impact microtubule dynamics and the G2/M phase of the cell cycle. We examined the effect of APC loss on expression of G2/M proteins, identifying a significant upregulation of CDK1 in APCKD cells. Despite no changes in phosphorylation status of CDK1, we found that Cyclin B1 and CDK1 are only complexed in the APCKD cells, suggesting increased activation. Further studies showed that while the majority of CDK1 and Cyclin B1 are localized to the cytoplasm, there is a small amount in the nucleus. Based on these findings, we sought to investigate whether PTX sensitivity would be altered in response to CDK1 inhibitor, RO-3306. We have shown that PTX resistant APCKD cells are more sensitive (IC50 = 25.5uM) to RO-3306 compared the parental control (IC50 = 78uM). Future studies will use combination and sequential treatments to monitor PTX response in vitro and in vivo. Combined, these studies are elucidating the mechanisms by which loss of APC controls sensitivity to PTX in TNBC, with the long-term goal of designing treatment regimens to improve patient health and survival. Citation Format: Jeni Prosperi, Emily Astarita, Camden Hoover, Sara Maloney. Apc control of taxane resistance in breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-21.

Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine whether there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and P < 5 × 10–8 was considered statistically significant. Genome-wide significant evidence of qualitative interaction was identified on chr2q21.3 in intron 5 of the transmembrane protein 163 (TMEM163) and upstream of the cyclin T2 (CCNT2). The most significant SNP using the Empirical Bayes method, in this region that included 45 significantly associated SNPs, was rs1818613 [per allele OR in never smokers 0.87, 95% confidence interval (CI), 0.82–0.93; former smokers 1.00, 95% CI, 0.91–1.07; current smokers 1.25, 95% CI 1.12–1.40, Pinteraction = 3.08 × 10–9). Examination of the Genotype-Tissue Expression Project data demonstrated an expression quantitative trait locus in this region for TMEM163 and CCNT2 in several tissue types. Colocalization analysis supported a shared SNP, rs842357, in high linkage disequilibrium with rs1818613 (r2 = 0. 94) driving both the observed interaction and the expression quantitative trait loci signals. Future studies are needed to confirm and understand the differential biologic mechanisms by smoking status that contribute to our PDAC findings. Significance: This large genome-wide interaction study identifies a susceptibility locus on 2q21.3 that significantly modified PDAC risk by smoking status, providing insight into smoking-associated PDAC, with implications for prevention.

Context Altered satiety hormones in women with polycystic ovarian syndrome (PCOS) may contribute to obesity. Diets with a low glycemic load (GL) may influence appetite-regulating hormones including glucagon and ghrelin. Objective To test the hypothesis that following a 4-week, eucaloric low vs high GL diet habituation, a low vs high GL meal will increase glucagon and decrease ghrelin to reflect greater satiety and improve self-reported fullness. Methods Secondary analysis of a randomized crossover trial. Participants Thirty women diagnosed with PCOS. Intervention Participants were provided low (41:19:40% energy from carbohydrate:protein:fat) and high (55:18:27) GL diets for 8 weeks each. At each diet midpoint, a solid meal test was administered to examine postprandial ghrelin, glucagon, glucose, insulin, and self-reported appetite scores. Results After 4 weeks, fasting glucagon was greater with the low vs high GL diet (P = .035), and higher fasting glucagon was associated with lesser feelings of hunger (P = .009). Significant diet effects indicate 4-hour glucagon was higher (P < .001) and ghrelin was lower (P = .009) after the low vs high GL meal. A trending time × diet interaction (P = .077) indicates feelings of fullness were greater in the early postprandial phase after the high GL meal, but no differences were observed the late postprandial phase. Conclusion These findings suggest after low GL diet habituation, a low GL meal reduces ghrelin and increases glucagon in women with PCOS. Further research is needed to determine the influence of diet composition on ad libitum intake in women with PCOS.

In recent years there has been an increasing interest in compressive imaging devices that capture spectral images with high spatial and spectral resolution with as few as a single snapshot. Nonetheless, there exists an intrinsic trade-off between spatial and spectral resolution which degrades one at the expense of the other. To alleviate this, state-of-art systems have relied on multiple snapshots attained via dynamically programmable spatial light modulators (SLM), or on side information from a second sensor attained via beam-splitters or stereo setups, which suffer from occlusion and demand registration tasks. This work proposes a compressive snapshot spectral imaging architecture that builds on the ideas of side information, but relies on a single image sensor. Specifically, we propose to split the incoming light into two paths, such as in a conventional interferometer, with one path dispersing the coded light, while the other just relaying it, so as to multiplex a traditional coded-and-dispersed measurement with a modulated grayscale version of the 3D cube in the image sensor. We have coined the latter, virtual side information. The proposed optical system is versatile in the sense that it can move from a fully-encoding system, to a spatially modulated grayscale camera, by switching/blocking the splitting response of the beam-splitters. Furthermore, we propose a computational algorithm to recover the underlying spectral cube exploiting the high spatial resolution provided by the virtual side information. We demonstrate through simulations from over fifty spectral images, and via an experimental proof-of-concept implementation, that the proposed imaging system together with the computational algorithm represents an efficient alternative to acquire spectral images without relying on additional sensors.

Background Numerous national and international studies have explored the issue of gender disparity in health science–publication rates. However, few have examined publication type (e.g., reviews and original research) and authorship order, which are 2 key factors in contribution recognition and the work’s visibility and application. Objective The objective of this work was to determine the changes in the distribution of women as first authors by publication type over time in pharmacy practice journals. Methods This was a bibliometric data analysis of pharmacy practice publications from January 2007 through December 2017. We used data from the U.S. Social Security Administration, and the multilingual Genderize application program interface (Genderize.io) to identify the authors’ potential gender. To determine the publication type, we used the Web of Science article list (Clarivate Analytics, Philadelphia, PA). The Cochran-Armitage trend test was used to determine the differences over time. Results Articles published from January 2007 through December 2017 in 8 pharmacy practice journals were reviewed (N = 14,658 articles): research articles (63.8%), reviews (17.0%), editorial material (11.1%), and letters (8.1%). There was a statistically significant increase in the number of first-authored articles and reviews by women (45.1% to 55.4% and 39.2% to 56.1%, respectively). There was not a significant increase in the proportion of women as first authors in editorials or letters over the study period. Conclusion Despite increases in research and reviews with women as first authors, there is still a need for increased representation of women in opinion-based publications such as editorials.

Epidural spinal cord stimulation has been reported to partially restore volitional movement and autonomic functions after motor and sensory-complete spinal cord injury (SCI). Modern spinal cord stimulation platforms offer significant flexibility in spatial and temporal parameters of stimulation delivered. Heterogeneity in SCI and injury-related symptoms necessitate stimulation personalization to maximally restore functions. However, the large multi-dimensional stimulation space makes exhaustive tests impossible. In this paper, we present a Bayesian optimization strategy for identifying personalized optimal stimulation patterns based on the participant's expressed preference for stimulation settings. We present companion validation protocols for investigating the credibility of learned preference models. The results obtained for five participants in the E-STAND spinal cord stimulation clinical trial are reported. Personalized preference models produced by the proposed learning and optimization algorithm show that there is more similarity in optimal frequency than in pulse width across participants. Across five participants, the average model prediction accuracy is 71.5% in internal cross-validation and 65.6% in prospective validation. Statistical tests of both validation studies show that the ability of the preference models to correctly predict unseen preference data is significantly greater than chance. The personalized preference models are also shown to be significantly correlated with motor task performance across participants. We show that several aspects in participants' quality of life has been improved over the course of the trial. Overall, the results indicate that the Bayesian preference optimization algorithm could assist clinicians in the systematic programming of individualized therapeutic stimulation settings and improve the therapeutic outcomes.

Background: Whether circulating polyunsaturated fatty acid (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome. Methods: We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case–Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data. Results: Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk [estimates per one SD increase in each PUFA-specific weighted genetic score using summary statistics: linoleic acid odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.98–1.02; arachidonic acid OR = 1.00, 95% CI = 0.99–1.01; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87–1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using individual-level data or summary statistics, or stratification by age and sex. Conclusions: Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk. Impact: These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer.

This study evaluated feasibility and acceptability of adding energy balance modeling displayed on weight graphs combined with a wrist-worn bite counting sensor against a traditional online behavioral weight loss program. Adults with a BMI of 27–45 kg/m2 (83.3% women) were randomized to receive a 12-week online behavioral weight loss program with 12 weeks of continued contact (n = 9; base program), the base program plus a graph of their actual and predicted weight change based on individualized physiological parameters (n = 7), or the base program, graph, and a Bite Counter device for monitoring and limiting eating (n = 8). Participants attended weekly clinic weigh-ins plus baseline, midway (12 weeks), and study culmination (24 weeks) assessments of feasibility, acceptability, weight, and behavioral outcomes. In terms of feasibility, participants completed online lessons (M = 7.04 of 12 possible lessons, SD = 4.02) and attended weigh-ins (M = 16.81 visits, SD = 7.24). Six-month retention appears highest among nomogram participants, and weigh-in attendance and lesson completion appear highest in Bite Counter participants. Acceptability was sufficient across groups. Bite Counter use (days with ≥ 2 eating episodes) was moderate (47.8%) and comparable to other studies. Participants lost 4.6% ± 4.5 of their initial body weight at 12 weeks and 4.5% ± 5.8 at 24 weeks. All conditions increased their total physical activity minutes and use of weight control strategies (behavioral outcomes). Although all groups lost weight and the study procedures were feasible, acceptability can be improved with advances in the technology. Participants were satisfied with the online program and nomograms, and future research on engagement, adherence, and integration with other owned devices is needed. ClinicalTrials.gov Identifier: NCT02857595

Financial and educational barriers significantly impact low socioeconomic status racial and ethnic minority groups in their pursuit of health care, though less is known about the interplay of these factors in the pursuit of surgical care. This study was designed to uncover the challenges to patient understanding and compliance with pre- and postsurgical clinical advice in low-income urban environments. The data for this study were collected in spoken survey with eighty patients in 9 surgery clinics at Temple University Hospital in Philadelphia. Survey responses were coded into various groups until categories emerged. Relationships among categories were identified to generate themes and subthemes. Key facilitators of patient understanding and compliance were physician likeability and communication. Eighty (100%) patients reported that the physician always treated them with respect, which was important in their interpretation of their experience with the physician. Eighteen (23%) patients identified a language other than English as their primary language and 57 (71%) patients completed high school or less schooling, which likely influenced their communication with the physician. Eighty (100%) patients expressed that the physician always explained things in a way they could understand, focusing on clarity and thoroughness. Challenges to patient understanding and compliance were finances and social resources. Patients noted difficulty paying for medical care and a lack of support at home. Agency could facilitate use of surgical care while a lack thereof could challenge motivation. Ultimately, these themes showed how patients in this environment interact with surgical care.

HIV testing among young Black MSM and transwomen (YBMSM/TW) is the gateway to biomedical HIV prevention or treatment. HIV self-testing (HST) is a method that may increase consistent HIV testing. TRUST, a brief, peer-based behavioral intervention, was designed to increase uptake of consistent (every three months) HST among YBMSM/TW in New York City. To test the efficacy of the intervention, we randomized 200 friend pairs into either the intervention condition (TRUST) or a time and attention control condition. A modified intent-to-treat analysis found that self-reported HST at 3-month follow-up was statistically significantly higher (uOR 2.29; 95% CI 1.15, 4.58) and at 6-month follow-up was marginally statistically significantly higher (uOR 1.94; 95% CI 1.00, 3.75) in the intervention arm as compared with the control arm. There were no statistically significant differences by arm at 9- or 12-month follow-up. TRUST, a culturally-congruent intervention to increase HST among YBMSM/TW, had short-term impact on past-three month HST. Clinical Trials Registration ClinicalTrial.gov NCT04210271.

Traumatic brain injury is the leading cause of morbidity and mortality for children in the United States. The aim of this study was to develop and implement a guideline to reduce radiation exposure in the pediatric head injury patient by identifying the patient population where repeat imaging is necessary and to establish rapid brain protocol magnetic resonance imaging as the first-line modality.A retrospective chart review of trauma patients between 0 and 14 y of age admitted at a pediatric level 2 trauma center was performed between January 2013 and June 2019. The guideline established the appropriateness of repeat scans for patients with Glasgow Coma Scale13 with clinical neurological deterioration or patients with Glasgow Coma Scale ≤13 and intracranial hemorrhagic lesion on initial head computed tomography (CT).Our trauma registry included 592 patients during the study period, 415 before implementation and 161 after implementation. A total of 132 patients met inclusion criteria, 116 pre-guideline and 16 post-guideline. The number of patients receiving repeat head CTs significantly decreased from 34.5% to 6.3% (P 0.02). There was also a significant decrease in the mean number of head CT/patient pre-guideline 1.63 (range 1-7) compared with post-guideline 1.06 (range 1-2) (P 0.02).CT head imaging is invaluable in the initial trauma evaluation of pediatric patients. However, it can be overused, and the radiation may lead to long-term deleterious effects. Establishing a head imaging guideline which limits use with clinical criteria can be effective in reducing radiation exposure without missing injuries.

Background: To investigate how changes in sedentary behavior relate to health outcomes, it is important to establish the test–retest reliability of activity monitors in measuring habitual sedentary behavior in people with type 2 diabetes (T2D) as a prerequisite for interpreting this information. Thus, the authors’ objective was to examine the test–retest reliability of a common activity monitor (activPAL™) in measuring sedentary behavior and physical activity in people with T2D. Methods: Sedentary-time, standing-time, stepping-time, step-count, and sit-to-stand transitions were obtained from two 7-day assessment periods separated by at least 1 week. Test–retest reliability was determined with the intraclass correlation coefficient (ICC) to compare sedentary and activity measures between the 2 time points. Results: A total of 30 participants with self-reported T2D completed the study (age 65 [6] y, 63% women, body mass index 33.3 [5] kg/m2). High test–retest reliability was found for sedentary-time (ICC = .79; 95% confidence interval [CI], .61–.89) and standing-time (ICC = .74; 95% CI, .53–.87). Very high test–retest reliability was found for stepping-time (ICC = .90; 95% CI, .81–.95), step-count (ICC = .91; 95% CI, .83–.96), and sit-to-stand transitions (ICC = .90; 95% CI, .79–.95). Conclusion: The activPAL™ device showed high to very high test–retest reliability in measuring all tested activity categories in people with T2D.

Prenatal diethylstilbestrol (DES) exposure is associated with increased risk of hormonally mediated cancers and other medical conditions. We evaluated the association between DES and risk of pancreatic cancer and pancreatic disorders, type 2 diabetes, and gallbladder disease, which may be involved with this malignancy. Our analyses used follow-up data from the US National Cancer Institute DES Combined Cohort Study. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age, sex, cohort, body mass index, smoking, and alcohol for the association between prenatal DES exposure and type 2 diabetes, gallbladder disease (mainly cholelithiasis), pancreatic disorders (mainly pancreatitis), and pancreatic cancer among 5667 exposed and 3315 unexposed individuals followed from 1990 to 2017. Standardized incidence rate (SIR) ratios for pancreatic cancer were based on age-, race-, and calendar year-specific general population cancer incidence rates. In women and men combined, the hazards for total pancreatic disorders and pancreatitis were greater in the prenatally DES exposed than the unexposed (HR = 11, 95% CI 2.6–51 and HR = 7.0, 95% CI 1.5–33, respectively). DES was not associated overall with gallbladder disease (HR = 1.2, 95% CI 0.88–1.5) or diabetes (HR = 1.1, 95% CI 0.9–1.2). In women, but not in men, DES exposure was associated with increased risk of pancreatic cancer compared with the unexposed (HR: 4.1, 95% CI 0.84–20) or general population (SIR: 1.9, 95% CI 1.0–3.2). Prenatal DES exposure may increase the risk of pancreatic disorders, including pancreatitis in women and men. The data suggested elevated pancreatic cancer risk in DES-exposed women, but not in exposed men.

Compressive multispectral imaging systems comprise a new generation of spectral imagers that capture coded projections of a scene where spectral data cubes are reconstructed computationally. Separately, time-of-flight (ToF) cameras obtain 2D range images where each pixel records the distance from the camera sensor to the target surface. The demand for these imaging modalities is rapidly increasing, and thus, there is strong interest in developing new image sensors that can simultaneously acquire multispectral-color-and-depth imagery (MS+D) using a single aperture. Work in this path has been mainly developed via RGB+D imaging. However, in RGB+D, the multispectral image is limited to three spectral channels, and the imaging system often relies on two image sensors. We recently proposed a compressive MS+D imaging device that used a digital-micromirror-device, requiring a bulky double imaging-and-relay path. To overcome the bulkiness and other difficulties of our previous imaging system, this work presents a more-compact MS+D imaging device with snapshot capabilities. It provides better spectral sensing, relying on a static color-coded-aperture (CCA) and a ToF sensor. To guarantee good quality in the recovery, we develop an optimization method for CCA based-on blue-noise-multitoning, solved via the direct-binary-search algorithm. A testbed-setup is reported along with simulated and real experiments that demonstrate the MS+D capabilities of the proposed system over static and dynamic scenes.

This study aims to determine the degree to which Portable Automated Rapid Testing (PART), a freely-available program running on a tablet computer, is capable of reproducing standard laboratory results. Undergraduate students were assigned to one of three within-subject conditions that examined repeatability of performance on a battery of psychoacoustical tests of temporal fine structure processing, spectro-temporal amplitude modulation, and targets in competition. The Repeatability condition examined test/retest with the same system, the Headphones condition examined the effects of varying headphones (passive and active noise-attenuating), and the Noise condition examined repeatability in the presence of recorded cafeteria noise. In general, performance on the test battery showed high repeatability, even across manipulated conditions, and was similar to that reported in the literature. These data serve as validation that suprathreshold psychoacoustical tests can be made accessible to run on consumer-grade hardware and performed in less controlled settings. This dataset also provides a distribution of thresholds that can be used as a normative baseline against which auditory dysfunction can be identified in future work.